This invention relates to the delivery of compounds through epithelial cell layers using impulse transients, i.e., stress waves.
Various methods have been employed for facilitating the delivery of pharmaceutical agents through the skin. One layer of the skin is the stratum corneum, which forms the outermost layer of the epidermis and is thought to act as the skin's primary barrier to molecular transport. It has a thickness of 10 to 15 .mu.m and is composed of layers of corneocytes, with the layers varying in thickness from 10 to 50 cells. Corneocytes are keratin-filled cells that lack nuclei and cytoplasmic organelles. Intercellular regions of the stratum corneum are composed mostly of neutral lipids and comprise 5 to 21% of the stratum corneum volume.
One method of delivering drugs through the skin is iontophoresis, in which electric current applied to the surface of the skin increases the penetration of charged drugs (Singh et al., Med. Re. Rev., 13:569, 1993). However, the efficiency of drug delivery using this method depends on the ionization state of the drug. In addition, because iontophoresis uses high current densities, it can burn the skin (Singh et al., supra).
In another method, phonophoresis, a drug is delivered through intact skin using ultrasound (Skauen et al., Intern. J. Pharm., 20:235, 1984; Mitragotri et al., J. Pharmaceut. Sci., 84:697, 1995). However, the tensile component of ultrasound waves (negative pressure), which is always present in ultrasound waves, can cause tissue injury (Ter Haar, Biological Effects of Ultrasound in Clinical Applications, In Ultrasound: Its Chemical, Physical, and Biological effects, Suslick, ed., VCH Publishers, pp. 305-20; 1988). In addition, the method requires long exposure to deliver a therapeutic dose of the drug.